American Heart Association Diet Research Articles

Food and Cardiovascular Disease: What to Eat and What Not to Eat

In 2019, the Global Burden of Disease study revealed alarming statistics regarding cardiovascular disease (CVD) in Pakistan. The estimated age-standardized incidence and death rates were 918.18 and 357.88 per 100,000 respectively, surpassing global averages.1 Notably, Pakistan faces unique challenges with a high prevalence of Rheumatic heart disease and early onset coronary artery disease.1
 The World Health Organization's 2021 factsheet underscores four pivotal modifiable behavioral risk factors for CVD and stroke: unhealthy diet, physical inactivity, tobacco use, and harmful alcohol consumption. These behaviors manifest in individuals as elevated blood pressure, glucose, lipids, and adverse body mass index, exacerbating cardiovascular risk.2 In Pakistan, the consumption of unhealthy foods and excessive calories significantly contributes to adverse cardiometabolic profiles, including obesity and dyslipidemia.2
 Recent research, such as that by Daruish Mozaffain et al. in "Food is Medicine," advocates for food-based interventions tailored to individual health conditions, ranging from medically tailored meals to nutritional and culinary education.3 However, Pakistani patients with CVD face challenges due to the lack of localized guidelines, educational resources, and accessible nutritionists. Shah et al.'s review underscores the importance of providing clear and culturally relevant dietary guidance for the local population.4
 Addressing these challenges requires the development of high-quality, culturally sensitive educational materials. These resources should be readily understandable, pictorial, and integrated into both inpatient and outpatient care. Local experts, including dietitians and researchers, can play a crucial role in creating tailored educational content. Figures 1 exemplify the efforts of these experts to provide practical guidance to the Pakistani population.4
 In conclusion, there is an urgent need for comprehensive, easy-to-understand patient education resources catering to the unique nutritional needs of Pakistani individuals with cardiovascular disease. By addressing these gaps, we can empower patients to make informed dietary choices and improve cardiovascular outcomes.
 References
 
 Samad Z, Hanif B. Cardiovascular Diseases in Pakistan: Imagining a Postpandemic, Postconflict Future. Circulation. 2023;147(17):1261-3.
 Liaquat A, Javed Q. Current trends of cardiovascular risk determinants in Pakistan. Cureus. 2018;10(10):e3409.
 Mozaffarian D, Aspry KE, Garfield K, Kris-Etherton P, Seligman H, Velarde GP, et al. “Food Is Medicine” Strategies for Nutrition Security and Cardiometabolic Health Equity: JACC State-of-the-Art Review. J Am Coll Cardiol. 2024;83(8):843-64.
 Shah SU, Waseem T, Afridi T, Shah MI. Nutritional Needs for Cardiovascular Health in Pakistani Population. Pak Heart J. 2022;55(2):101-13.
 American Heart Association. Lifestyle Changes for Heart Failure. Accessed on March 30, 2024. Available at: https://www.heart.org/en/health-topics/heart-failure/treatment-options-for-heart-failure/lifestyle-changes-for-heart-failure
 American Diabetes Association. What superstar foods are good for diabetes? Accessed on March 30, 2024. Available at: https://diabetes.org/food-nutrition/food-and-blood-sugar/diabetes-superstar-foods
 American Heart Association. The American Heart Association Diet and Lifestyle Recommendations. Accessed on March 30, 2024. Available at: https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/nutrition-basics/aha-diet-and-lifestyle-recommendations
 American Heart Association. Managing Blood Pressure with a Heart-Healthy Diet. Accessed on March 30, 2024. Available at: https://www.heart.org/en/health-topics/high-blood-pressure/changes-you-can-make-to-manage-high-blood-pressure/managing-blood-pressure-with-a-heart-healthy-diet

A modified Mediterranean‐ketogenic diet favorably modulates the metabolic profiles of mild cognitively impaired individuals

AbstractBackgroundImpaired glucose utilization is central to the pathogenesis of Alzheimer’s disease. In a hypometabolic state, the brain depends on alternative sources of energy, including amino acids, fatty acids, and ketone bodies (KBs). As KBs can cross the blood‐brain barrier, it is considered that a ketogenic diet could augment the high energetic demand of the central nervous system (CNS). A ketogenic diet is already a part of clinical care in epilepsy a CNS disorder. However, the holistic benefits of this diet for Alzheimer’s remain to be determined.MethodsA randomized crossover pilot trial was conducted where participants consumed either the Modified Mediterranean‐Ketogenic Diet (MMKD) or the American Heart Association Diet (AHAD) for 6 weeks, followed by a 6‐week washout, after which the respective other diet was consumed for 6 weeks. The cohort included both mild cognitively impaired (MCI) and cognitively normal (CN) individuals. Serum and cerebrospinal fluid (CSF) samples of these individuals were profiled using two metabolic platforms: MS‐based and NMR‐based metabolomics. Diet‐related changes in levels of metabolites were determined using linear‐mixed effect models with age and sex as confounders.ResultsWe identified post‐diet changes in the two diet groups (AHAD and MMKD), two cognitive groups (MCI and CN), and two fluids (serum and CSF). AHAD was associated with a decrease in serum levels of only a single metabolite, glutamine. MMKD led to widespread lipidomic and metabolic changes in the serum of mild cognitively impaired individuals. Remarkably, MMKD was associated with the reversal of AD‐related metabolic alterations identified in large cohorts like ADNI, AIBL, ROS/MAP, and signature for incident dementia in large epidemiological studies. The post‐MMKD changes include correcting metabolic dysregulation in branched‐chain amino acids, triglycerides, and plasmalogens a class of lipids implicated in membrane structure and function. Peripheral‐central metabolic correlations will be shared.ConclusionOur findings highlight the potential of dietary interventions, specifically the MMKD, in improving the cognitive and metabolic state of individuals with MCI. Further investigation is needed to capture the entirety of MMKD‐related modulation in metabolic profiles and the resulting benefit for AD.

Ketogenic Dietary Effects on Sleep, Cognition and Behavior in MCI: Baseline Sleep Results

AbstractBackgroundSleep disturbances in dementia occur often, are reported as neuropsychiatric symptoms, and are associated with higher caregiver burden and institutionalization. In mild cognitive impairment (MCI), sleep changes co‐occur with increasing neuropsychiatric symptoms and cognitive decline. Diet quality, like sleep, is a modifiable risk factor for Alzheimer’s disease. It is unknown how dietary interventions may impact sleep quality. This controlled clinical trial investigates for the first time a modified Mediterranean ketogenic diet (MMKD) compared to a low‐fat American Heart Association diet (AHAD) over 4 months on multiple sleep indices in adults with amnestic MCI. Here we report our baseline sleep findings.MethodThe WatchPAT Central Plus, an FDA approved home sleep test, was used to assess sleep quality. The WatchPAT quantifies numerous measures including total sleep time, pulse and sleep efficiency. Sleep‐disordered breathing is measured via the apnea‐hypopnea index (AHI) and oxygen‐desaturation index (ODI). Time spent in sleep stages is also quantified along with full night oxygen saturation and pulse rate. Independent samples t‐tests compared baseline sleep differences among male and female MCI participants.ResultA total of 64 MCI participants completed the baseline sleep assessments (mean age 70.2±7.0, BMI 27.0±4.3; 64.1% women). Mean sleep duration was 6 hrs46 min and 83.9% sleep efficiency. Mean AHI was 17.3±12.2 and mean ODI was 8.2±7.5 measured as >3% 02 desaturations, indicating on average moderate severity sleep apnea (AHI>15). Overnight sleep percentage by sleep stage (estimated from heart rate and accelerometer) averaged 15.4% in deep sleep and 22.3% in REM sleep. Mean REM latency was 105 minutes. Oxygen saturation averaged 94% and pulse, 61 bpm. Women had higher resting pulse (64.3bpm, p<.001). Sleep measures did not significantly differ by sex.ConclusionThe MCI sample, on average, had moderate severity sleep apnea at baseline, with sleep duration and efficiency slightly below standard recommendations of 7‐8 hours and efficiency > 85%, respectively. Future work will compare longitudinal changes in sleep quality across diet intervention groups. Understanding potential therapeutic effects of the MMKD on sleep quality and cognitive change will be vital in adding to the portfolio of targeted non‐pharmacological interventions for Alzheimer’s disease prevention.

Women’s Adherence to Healthy Dietary Patterns and Outcomes of Infertility Treatment

Increasing evidence suggests that specific foods and nutrients may improve infertility treatment outcomes in women. However, less is known about the role of dietary patterns. To investigate whether women's adherence to a priori-defined dietary patterns promoted for the prevention of chronic conditions is associated with outcomes of infertility treatment. This prospective cohort study was conducted at a fertility center at an academic medical center in Boston, Massachusetts. Women undergoing infertility treatment cycles, including intrauterine insemination cycles and in vitro fertilization with or without intracytoplasmic sperm injection were included. Data were collected from January 2007 to October 2019, and data were analyzed from February to December 2022. Women's pretreatment diet was assessed with a validated food frequency questionnaire from which 8 a priori-defined scores were calculated (higher score indicates greater adherence): (1) Trichopoulou Mediterranean diet, (2) alternate Mediterranean diet, (3) Panagiotakos Mediterranean diet, (4) Healthy Eating Index, (5) Alternate Healthy Eating Index, (6) American Heart Association (AHA) index, (7) Dietary Approaches to Stop Hypertension index, and (8) plant-based diet. The adjusted probability of clinically relevant outcomes (live birth as a primary outcome and clinical pregnancy and pregnancy loss as secondary outcomes) was evaluated across quartiles of adherence to each dietary pattern using multivariable generalized linear mixed models to account for repeated cycles. This analysis included 612 women with a median (IQR) age of 35.0 (32.0-38.0) years. There was no association between women's adherence to the 8 a priori dietary patterns and probability of clinical pregnancy or live birth following in vitro fertilization or intrauterine insemination. However, an inverse association was found between adherence to AHA dietary pattern and risks of total and clinical pregnancy loss. Among women who became pregnant during the course of infertility treatment, the adjusted probabilities of pregnancy loss in the lowest and highest quartile of the AHA dietary pattern were 0.41 (95% CI, 0.33-0.50) and 0.28 (95% CI, 0.21-0.36), respectively (P for trend = .02). The corresponding adjusted probabilities of clinical pregnancy loss were 0.30 (95% CI, 0.22-0.39) and 0.15 (95% CI, 0.10-0.23) (P for trend = .007). A similar pattern was observed for all other dietary patterns, with the exception of the plant-based diet pattern. Findings of this cohort study suggest that preconception adherence to the AHA diet may be associated with a lower likelihood of pregnancy loss during the course of infertility treatment.

Effects of a ketogenic and low-fat diet on the human metabolome, microbiome, and foodome in adults at risk for Alzheimer's disease.

The ketogenic diet (KD) is an intriguing therapeutic candidate for Alzheimer's disease (AD) given its protective effects against metabolic dysregulation and seizures. Gut microbiota are essential for KD-mediated neuroprotection against seizures as well as modulation of bile acids, which play a major role in cholesterol metabolism. These relationships motivated our analysis of gut microbiota and metabolites related to cognitive status following a controlled KD intervention compared with a low-fat-diet intervention. Prediabetic adults, either with mild cognitive impairment (MCI) or cognitively normal (CN), were placed on either a low-fat American Heart Association diet or high-fat modified Mediterranean KD (MMKD) for 6 weeks; then, after a 6-week washout period, they crossed over to the alternate diet. We collected stool samples for shotgun metagenomics and untargeted metabolomics at five time points to investigate individuals' microbiome and metabolome throughout the dietary interventions. Participants with MCI on the MMKD had lower levels of GABA-producing microbes Alistipes sp. CAG:514 and GABA, and higher levels of GABA-regulating microbes Akkermansia muciniphila. MCI individuals with curcumin in their diet had lower levels of bile salt hydrolase-containing microbes and an altered bile acid pool, suggesting reduced gut motility. Our results suggest that the MMKD may benefit adults with MCI through modulation of GABA levels and gut-transit time.

Small extracellular vesicles in plasma reveal molecular effects of modified Mediterranean-ketogenic diet in participants with mild cognitive impairment.

Extracellular vesicles have emerged as a less-invasive nano-tool for discovering biomarkers of Alzheimer's disease and related dementia. Here, we analysed different neuron-enriched extracellular vesicles from plasma to predict response and molecular mechanisms of ketogenic diet's efficacy in mild cognitive impairment participants. The study was a randomized crossover design in which cognitively normal and mild cognitive impairment participants consumed a modified Mediterranean-ketogenic diet or American Heart Association diet for 6 weeks, followed by other diet after washout. L1 cell adhesion molecule, synaptophysin and neural cell adhesion molecule surface markers were used to enrich for neuron-secreted small extracellular vesicles (sEVL1CAM, sEVSYP and sEVNCAM). For the first time, we have presented multiple evidences, including immunogold labelling/transmission electron microscopy, clusters of differentiation 63-ELISA-based assay, confocal microscopy fluorescent images and flow cytometry data confirming the presence of L1 cell adhesion molecule on the surface of sEVL1CAM, validating purity and relative abundance of sEVL1CAM in the plasma. Cargo analysis of sEVL1CAM showed that modified Mediterranean-ketogenic diet intervention reduces amyloid beta 1-42 (50.3%, P = 0.011), p181-tau (34.9%, P = 0.033) and neurofilament light (54.2%, P = 0.020) in mild cognitive impairment participants. Moreover, sEVL1CAMshowed better sensitivity compared with CSF in analysing increased glutamate (6-folds, P < 0.0001) from mild cognitive impairment participants following modified Mediterranean-ketogenic diet intervention. sEVL1CAM characterization also suggested that modified Mediterranean-ketogenic diet differentially targets the expression of various glutamate receptors-glutamate receptor ionotropic NMDA1, glutamate receptor ionotropic NMDA2A, glutamate receptor ionotropic NMDA2B and glutamate receptor ionotropic AMPA type subunit 1. Importantly, these sEVL1CAM measures strongly correlated with corresponding clinical CSF biomarkers (neurogranin, amyloid beta 1-42, neurofilament light and tau). Furthermore, sEVL1CAM were loaded with less advanced glycation endproducts and exhibited anti-inflammatory activity following modified Mediterranean-ketogenic diet intervention. Most importantly, the expression of monocarboxylate transporter 2 on the surface of sEVL1CAM predicted the amyloid beta 1-42 response to modified Mediterranean-ketogenic diet intervention (area under the curve = 0.87, P = 0.0044) and offered a novel screening tool to identify participants responsive to this dietary intervention. Finally, sEVL1CAM, sEVSYP and sEVNCAM showed significantly high concordance in analysing amyloid beta 1-42 (Pearson correlation coefficient ≥ 0.63, P < 0.01) and neurofilament light (Pearson correlation coefficient ≥ 0.49, P < 0.05). Together, small extracellular vesicles in plasma offers promise in assessing the efficacy of dietary/therapeutic intervention against mild cognitive impairment/Alzheimer's disease.

Changes in Adiposity and Cerebrospinal Fluid Biomarkers Following a Modified Mediterranean Ketogenic Diet in Older Adults at Risk for Alzheimer's Disease.

BackgroundKetogenic diets have been used to treat both obesity and neurological disorders, including epilepsy and more recently Alzheimer’s disease (AD), likely due to favorable effects on both central and peripheral metabolism. Improvements in body composition have also been reported; however, it is unclear if diet-induced changes in adiposity are related to improvements in AD and related neuropathology.PurposeWe examined the effects of a Modified Mediterranean Ketogenic (MMK) diet vs. an American Heart Association (AHA) diet on body weight, body composition, and body fat distribution and their association with cerebrospinal fluid (CSF) biomarkers in older adults at risk for AD.MethodsTwenty adults (mean age: 64.3 ± 6.3 years, 35% Black, 75% female) were randomly assigned to a crossover trial starting with either the MMK or AHA diet for 6 weeks, followed by a 6-week washout and then the opposite diet for 6 weeks. At baseline and after each diet adiposity was assessed by dual-energy x-ray absorptiometry and CSF biomarkers were measured. Linear mixed effect models were used to examine the effect of diet on adiposity. Spearman correlations were examined to assess associations between adiposity and CSF biomarkers.ResultsAt baseline there was a high prevalence of overweight/obesity and central adiposity, and higher visceral fat and lower peripheral fat were associated with an adverse CSF biomarker profile. The MMK and AHA diets led to similar improvements in body composition and body fat distribution. Significant correlations were found between changes in adiposity and changes in CSF biomarkers (r’s = 0.63–0.92, p’s < 0.05), with notable differences by diet. Decreases in body fat on the MMK diet were related to changes in Aβ biomarkers, whereas decreases in body fat on the AHA diet were related to changes in tau biomarkers and cholinesterase activity. Interestingly, increases in CSF Aβ on the MMK diet occurred in those with less fat loss.ConclusionAn MMK diet leads to favorable changes in body composition, body fat distribution, and CSF biomarkers. Our data suggest that modest weight loss that maximizes visceral fat loss and preserves peripheral fat, may have the greatest impact on brain health.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT02984540].

Feasibility and Effectiveness of a Multi-Micronutrient Intervention as a Palliative Care Therapy in Patients With Congestive Heart Failure

ObjectivesVeterans with HF are at risk of micronutrient depletion due to combined systemic disease and drug induced altered nutrient disposition. This pilot aimed to test feasibility and effectiveness of a MMI to improve micronutrient status, cardiac function and quality of life in Veterans with HF. MethodsA pre/post repeated measures design was used. Veterans with stable HF stage B-D, left ventricular ejection fraction (LVEF) ≤45%, from ischemic cardiomyopathy with systolic dysfunction were recruited. The 6-month MMI was 3 tabs daily providing thiamin (B1) 100 mg, 50 mg each of riboflavin, niacin, pantothenic acid, pyridoxine (B6), inositol, 25 mg phosphatidyl choline, 400 mcg folic acid, and 50 mcg each of B12 and biotin, and 50 mg elemental zinc (Zn). Ergocalciferol was given as 50,000 IU weekly for 2 months then every 2 weeks for 4 months. Micronutrient status and LVEF (echocardiogram) were determined as least-squares mean (± standard error, SE) estimated from general linear mixed effect models fitted to micronutrient measurements adjusting for age (18–65 Vs. > 65); feasibility of MMI assessed as % consumed. ResultsThis abstract focuses on the nutrient status at baseline, feasibility of the MMI, and change in nutrient status following MMI. Twenty-two male Veterans (86% Caucasian), median 64 years (59–75 interquartile range, IQR) started MMI; 20 completed. At baseline, median (IQR) dietary intake was 1639 (1472–1838) calories, 36 (28–41) % fat, 13 (10–15) % saturated fat, 2981 (2067–3534) mg sodium while following the American Heart Association diet with 2 gm sodium restriction. Micronutrient intake was 1.2 (0.9–1.4) mg B1, 1.2 (1.0–1.8) mg B6, 49 (38–166) IU Vitamin D, and 7 (5–10) mg zinc. Median % compliance with MMI at 3 and 6 months was ≥ 92 and ≥94, respectively. Baseline and changes in blood measures of micronutrients were: B1, 119 (SE 13) and 96 (SE 20, p< 0.0001) nmol/L; B6, 11.4 (SE 6.3) and 57.3 (SE 9.2, p< 0.0001) ng/mL; total 25-OH Vitamin D, 31.2 (SE 2.3) and 6.5 (SE 3.4, p = 0.057) ng/mL; Zn, 81.4 (SE 5.1) and 13.8 (7.6, p = 0.07) mcg/dL. LVEF at baseline and 6 months were 28.9 (SE 1.6) % and 30.0 (SE 1.7) %, respectively (p = 0.64). ConclusionsThe feasibility of adding MMI to complex pharmaceutical regimens in male Veterans with stable HF was high. MMI was effective in improving micronutrient status and preserved LVEF. Funding SourcesDepartment of Veterans Affairs

A nutrigenetic tool for precision dietary management of non-alcoholic fatty liver disease deeming insulin resistance markers.

Non-alcoholic fatty liver disease (NAFLD) development is linked to insulin resistance and influenced by environmental factors, but it also underlined a genetic predisposition. The aim of this research was to build a predictive model based on genetic and hepatic health information, deeming insulin resistance markers in order to personalize dietary treatment in overweight/obese subjects with NAFLD. A 6-month nutritional intervention was conducted in 86 overweight/obese volunteers with NAFLD randomly assigned to 2 energy-restricted diets: the American Heart Association (AHA) diet and the Fatty Liver in Obesity (FLiO) diet. Individuals were genotyped using a predesigned panel of 95 genetic variants. A Genetic Risk Score (GRS) for each diet was computed using statistically relevant SNPs for the change on Fatty Liver Index (FLI) after 6-months of nutritional intervention. Body composition, liver injury and insulin resistance markers, as well as physical activity and dietary intake were also assessed. Under energy restriction, both the AHA and FLiO diets induced similar significant improvements on body composition, insulin resistance markers, hepatic health and dietary and lifestyle outcomes. The calculated score included in the linear mixed regression model was able to predict the change of FLI adjusted by diet, age and sex. This model allowed to personalize the most suitable diet for 72% of the volunteers. Similar models were also able to predict the changes on Triglycerides and Glucose (TyG) Index and retinol-binding protein 4 (RBP4) levels depending on diet. Models integrating genetic screening and insulin resistance markers can be useful for the personalization of NAFLD weight loss treatments.

Absolute and Relative Agreement between the Current and Modified Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) and the American Heart Association Healthy Diet Score (AHA-DS) in Post Myocardial Infarction Patients.

The American Heart Association Diet Score (AHA-DS) defines the cardiovascular health, and the Brazilian Cardioprotective Nutritional Program Dietary Index (BALANCE DI) was designed to evaluate diet quality in secondary cardiovascular prevention settings. Our aim was to assess the absolute and relative agreement between both tools in Brazilian adults after a myocardial infarction (MI). In this cross-sectional study, 473 individuals were included and had their diet assessed by a 24 h food recall and a semi-quantitative Food Frequency Questionnaire. The weighted Kappa between BALANCE DI and primary AHA-DS was 0.66 (95% CI: 0.08–0.21), and between BALANCE DI and total AHA-DS was 0.70 (95% CI: 0.20–0.32). To improve the agreement between the tools, modifications were made to the BALANCE DI scoring system. The weighted Kappa between New BALANCE DI and primary AHA-DS was 0.77 (95% CI: 0.36–0.48), and between BALANCE DI and total AHA-DS was 0.76 (95% CI: 0.34–0.46). The mean bias observed between the New BALANCE DI as compared to the primary and total AHA-DS was −16% (−51 to 19) and −8% (−41 to 24), respectively. Our results suggest that the New BALANCE DI may be a useful tool to evaluate diet quality in post MI patients.

Ketogenic dietary lifestyle intervention effects on sleep, cognition, and behavior in mild cognitive impairment: Study design.

IntroductionSleep and diet are modifiable risk factors for Alzheimer's disease (AD) that may be salient areas for the development of preventive intervention strategies against dementia in people with mild cognitive impairment (MCI). Sleep disturbances account for up to 15% of the population attributable risk for AD. Diet influences sleep quality, such that diets high in sugars, fat, and processed food affect sleep quality and cognition in older adults. The combination of poor sleep and diet health may increase risk for dementia in people with MCI, yet it is unknown how intervening on diet may influence sleep health.MethodsThe MCI Sleep Study assesses longitudinal changes in objective and subjective measures of sleep between two investigational diet groups in the Brain Energy for Amyloid Transformation in Alzheimer's Disease study: the modified Mediterranean ketogenic diet (MMKD) and the American Heart Association diet. Objective sleep assessments include an in‐home sleep study using the WatchPAT Central Plus (Itamar Medical, Ltd) at baseline and the end of the 4‐month diet intervention. Subjective sleep questionnaires include the Epworth Sleepiness Scale and Pittsburgh Sleep Quality Index. The MCI Sleep Study outcome measures include longitudinal change in cognitive performance, mood, behavior, and quality of life.ResultsStudy recruitment is currently ongoing. We hypothesize the low‐carb MMKD diet to have a beneficial impact on sleep health in individuals with MCI. Pre‐ and post‐diet changes in sleep metrics across diet groups will be examined using mixed effects analysis of variance models.DiscussionEarly assessment of chronic sleep and diet behaviors may be vital in understanding when interventions are necessary and the lifestyle modifications that should accompany future AD prevention and therapy recommendations.

Assessing the effect of modified Mediterranean‐ketogenic diet on mild cognitive impairment patients through plasma neuron‐derived exosomes

AbstractBackgroundRecently, we compared the effect of a high‐fat and low‐carb Modified Mediterranean‐Ketogenic Diet (MMKD) and a low‐fat American Heart Association Diet (AHAD) on 11 cognitively normal (CN) and 9 with mild cognitive impairment (MCI) older adults as a suggestive preventative intervention for Alzheimer’s disease (AD). We reported the promising effect of the MMKD on MCI patients as it was well‐tolerated and associated with increased cerebrospinal fluid (CSF) Aβ1‐42, decreased tau, and increased cerebral perfusion. Here, we characterized the plasma neuron‐derived exosomes (NDE) to further understand the molecular mechanisms underlying the efficacy of the MMKD against MCI.MethodThe completed study consisted of a randomized crossover design in which participants (both CN and MCI) consumed either the MMKD or the control AHAD for six weeks. Total exosomes (TE) were isolated from plasma by precipitation method, and NDE were enriched using Biotin‐tagged CD171 antibody attached with streptavidin‐magnetic beads. The purity, concentration, and size of TE and NDE were assessed by flow cytometry, nanoparticle tracking, immunogold‐labeling, electron microscopy, and exosome antibody array. NDE was characterized for several AD and neurodegeneration‐related biomarkers, advanced glycation endproducts (AGEs), glutamate, glutamate receptors, and β‐hydroxybutyrate (BHB) by ELISA and colorimetric assays. NDE effect on NF‐kB activity in human monocytes was studied as a molecular surrogate for inflammation.ResultWe confirmed the size, shape, and purity of both TE and NDE by multiple methods. Importantly, the MMKD treatment strongly reduced the level of Aβ1‐42 (by 50%, p=0.001), p(181)Tau (by 17%), and neurofilament L (by 55%, p=0.03) in the MCI group, but not with AHAD. MMKD reduced the AGEs in both CN and MCI groups and strongly increased the glutamate level in NDEs from the MCI group (6 fold, p&lt;0.001) but did not affect glutamate in CSF. The MMKD also modulated the expression of various glutamate receptors (GRIN1, GRIA1, GRIN2A, and GRIN2b). Interestingly, we detected BHB in NDEs, though no significant change was observed. MMKD inhibited the NF‐κB activity in monocytes suggesting a strong anti‐inflammatory effect.ConclusionNDE offers a promising peripheral measure to assess the efficacy and molecular mechanism of MMKD action against MCI.

Modified Mediterranean ketogenic diet resolves default mode network connectivity differences between adults with normal and impaired cognition

AbstractBackgroundIn the absence of disease modifying/preventative therapy for Alzheimer’s disease (AD), there has been increased focus on alternate therapeutic approaches, including the ketogenic diet, which supplies auxiliary metabolic fuel to brain and has potential neuroprotective effects. Our goal was to examine the modified Mediterranean‐ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) in older adults at risk for AD with respect to cognitive performance and associated brain functional connectivity within the default mode network (DMN), which has been implicated in cognitive processes directed toward the self, such as introspection and autobiographic memory.MethodEighteen participants with normal cognition and subjective memory complaints (SMC) (n = 10, mean age = 65 ± 7) or Mild Cognitive Impairment (MCI) (n = 8, mean age = 64 ± 4) completed six weeks on both diets in a randomized crossover design. Before and after each diet, participants underwent 3T brain MRI and cognitive testing. MRI included T1‐weighted imaging for gray/white matter segmentation, and blood oxygen level dependent (BOLD) imaging for resting‐state functional connectivity. Cognitive function was evaluated using two memory tests, the Free and Cued Selective Reminding Test (FCSRT) and story recall, which were composited into a single memory score. BOLD data were pre‐processed and de‐noised using standard techniques, and normalized to the Mayo Clinic Adult Lifespan Template (MCALT). Connectivity analyses were performed using CONN functional connectivity toolbox. Briefly, functional connectivity of the DMN was analyzed utilizing the PCC for a seed to voxel connectivity analysis.ResultAt baseline, there were statistically significant differences in DMN connectivity between MCI and cognitively normal participants with SMC (Figure‐1), with connectivity increases between DMN and superior frontal gyrus, and decreases between DMN and superior parietal gyrus, which were significantly correlated with baseline memory scores (Figure‐2). After both diets, there were no detectable differences in DMN connectivity between the two groups. However, MMKD had a more pronounced effect on reducing DMN hyper‐connectivity among MCI participants than AHAD (Figure‐3).ConclusionOur results suggest that a ketogenic intervention may augment aberrant DMN network connectivity patterns in adults at risk for AD and lessen cognitive decline.

Trends in Food Sources and Diet Quality Among US Children and Adults, 2003-2018

Time trends and population disparities in nutritional quality of foods from major US sources, including grocery stores, restaurants, schools, worksites, and other sources, are not well established. To investigate patterns and trends in diet quality by food sources among US children and adults overall and in sociodemographic subgroups. This serial, cross-sectional survey study included respondents from 8 National Health and Nutrition Examination Survey cycles (2003-2018) with valid dietary recalls. Data were analyzed from April 16, 2020, to July 20, 2020. Survey cycle, food source, and key sociodemographic subgroups. Mean diet quality of foods (meals, snacks, and beverages) consumed per person, characterized by the American Heart Association diet score (range, 0-80, with higher scores indicating healthier diets), the Healthy Eating Index 2015 (range, 0-100, with higher scores indicating healthier diets), and their components. For the American Heart Association diet score, poor diet was defined as less than 40.0% adherence (score, <32.0), intermediate diet as 40.0% to 79.9% adherence (score, 32.0-63.9), and ideal as 80.0% or greater adherence (score, ≥64.0). The study included 20 905 children 5 to 19 years of age (mean [SD] age, 12.1 [5.24] years; 51.0% male) and 39 757 adults 20 years or older (mean [SD] age, 47.3 [15.1] years; 51.9% female). Diet quality of foods consumed from grocery stores increased modestly in children (53.2% to 45.1% with poor diet quality; P = .006 for trend) and adults (40.1% to 32.9% with poor diet quality; P = .001 for trend), with smaller changes for restaurants among children (84.8% to 79.6% with poor diet quality; P = .003 for trend). Changes for restaurants among adults were not statistically significant (65.4% to 65.2% with poor diet quality; P = .07 with poor diet quality); the same was true of worksites (adults: 55.6% to 50.7% with poor diet quality; P = .25 for trend). Food quality from other sources worsened (children: 40.0% to 51.7% with poor diet quality; adults: 33.8% to 43.8% with poor diet quality; P < .001 for trend each). The largest improvement in diet quality was in schools, with the percentage with poor diet quality decreasing from 55.6% to 24.4% (P < .001 for trend), mostly after 2010, and with equitable improvements across population subgroups. Findings were similar for Healthy Eating Index 2015. Significant disparities in diet quality trends were seen by sex, race/ethnicity, educational level, and household income for food consumed from grocery stores. For example, the proportion of foods consumed from grocery stores that were of poor diet quality decreased among high-income adults (from 36.9% to 26.5%; P = .001 for trend) but not among low-income adults (from 45.8% to 41.3%; P = .09 for trend). By 2017-2018, foods consumed at schools improved significantly and provided the best mean diet quality of major US food sources, without population disparities. Additional improvements are needed from all major US food sources, with particular attention on equity.

The ketogenic diet as a potential prevention or therapeutic strategy for AD

AbstractBackgroundDiet is a powerful modulator of brain health. The ketogenic diet (KD), a very low carbohydrate diet, is remarkably effective in treating refractory epilepsy; 50‐70% of patients have &gt;50% seizure reduction and 30% have &gt;90% seizure reduction. Although the mechanisms underlying its effectiveness are not definitively known, reduction of neuronal hyperexcitability and neuroprotective effects of ketones have been demonstrated, as has reduction in AD pathology in rodent models. We tested the effect of a 6‐week Modified Mediterranean‐like KD (MMKD) compared with a low‐fat American Heart Association Diet (AHAD) on AD biomarkers and memory.MethodThe study used a randomized crossover design in which participants consumed either a MMKD (5‐10% of total daily calories obtained from carbohydrates) or the control AHAD (∼15% of calories obtained from fat per day) for 6 weeks, followed by a 6‐week washout period during which participants were instructed to resume their pre‐study diet, after which the second diet was consumed for 6 weeks. Diets were equicaloric with participants’ normal diet. Compliance was verified by measuring blood ketone levels. CSF collection, pseudocontinuous arterial spin label (pcASL) MRI, 11C‐AcAc/18F FDG Positron Emission Tomography (PET), and memory testing (Z score composite constructed from Story Recall and Free and Cued Selective Reminding Test) were performed at baseline and at the end of each intervention.ResultA total of 20 participants completed both diets, with 3 participants discontinuing the study early. Mean compliance rates for completers were 90% for the MMKD and 95% for AHAD. The MMKD was associated with increased CSF Aβ42 and decreased tau. Cerebral perfusion increased after the MMKD in AD regions of interest, and whole‐brain ketone uptake increased on 11C‐AcAc PET. No changes in these outcomes were observed following the AHAD. Memory performance improved after both diets.ConclusionThe MKKD intervention favorably influenced CSF AD biomarkers, cerebral perfusion, and memory. These results provide the basis for an ongoing Phase II study using a longer intervention in a larger sample of adults with MCI.

Prepregnancy adherence to dietary recommendations for the prevention of cardiovascular disease in relation to risk of hypertensive disorders of pregnancy

It is unclear whether adherence to diet recommendations for the prevention of cardiovascular disease (CVD) in the general population is also related to the risk of hypertensive disorders of pregnancy, including pre-eclampsia and gestational hypertension (GHTN). The aim was to evaluate the relation of prepregnancy adherence to the American Heart Association (AHA) diet recommendations and the Dietary Approaches to Stop Hypertension (DASH) with the risk of pre-eclampsia and GHTN. Between 1991 and 2009, we prospectively followed 16,892 singleton pregnancies among 11,535 women who participated in the Nurses' Health Study II. Prepregnancy diet was assessed every 4 y, from which we calculated dietary pattern scores from the DASH diet (8 components) and the diet recommendations from the AHA 2020 Strategic Impact Goals (primary score: 5 components; secondary score: primary score plus 3 components). Pregnancy outcomes were self-reported, and we estimated the RR (95% CI) of pre-eclampsia and GHTN with log-binomial regression using generalized estimating equations to account for repeat pregnancies and adjusting for potential confounders. Women had a mean (SD) age of 34.4 (34.0) y at pregnancy. Pre-eclampsia was reported in 495 (2.9%) pregnancies and GHTN in 561 (3.3%) pregnancies. The RR (95% CI) of pre-eclampsia for women in the highest quintile of the DASH was 0.65 (0.48, 0.87) compared with women in the lowest score quintile. A similar inverse trend was observed for the AHA primary (0.74; 95% CI: 0.55, 1.00) and secondary (0.81; 95% CI: 0.61, 1.07) scores comparing women in the highest versus the lowest score quintile. Neither the DASH nor the AHA scores were related to GHTN. Women with higher adherence to dietary recommendations for the prevention of CVD in the general population had a lower risk of pre-eclampsia-a common pregnancy complication related to higher CVD risk among women-than women with lower adherence to these recommendations.

Abstract 17285: Metabolite-Derived Network Reveals Cluster of Acylcholine Metabolites Associated With Better Diet Quality and Lower Prevalence of Type 2 Diabetes: Findings From the Boston Puerto Rican Health Study

Introduction: Puerto Rican (PR) adults living on the US mainland are at high risk for developing type 2 diabetes (T2D), and dietary factors may contribute to this increased risk. Network analysis is a data-reduction tool that can identify correlated clusters of co-regulated metabolites that reflect mechanisms underlying diet-T2D associations. Hypothesis: Diet quality will associate with T2D-associated metabolite clusters among PR adults. Methods: We used LC/MS to measure fasting plasma metabolites (&gt;700) among Boston PR Health Study participants, aged 45-75 years, with (n=258) and without (n=421) T2D. We applied an unsupervised correlation network-based method to identify metabolite clusters within a global metabolite network and calculated a score for each cluster using a weighted sum of metabolite concentrations. To estimate diet quality, we calculated a modified version of a previously validated American Heart Association diet score (AHA-DS). Logistic regression was used to assess cross-sectional associations between metabolite clusters and prevalent T2D, and linear regression was used to assess associations between the continuous AHA-DS and T2D-associated metabolite clusters among controls, adjusting for potential confounders and correcting for multiple testing. Results: We identified 7 metabolite clusters that were associated with prevalent T2D ( p &lt;0.05). For every 1-standard deviation (SD) increase in cluster score, the odds ratios for prevalent T2D and 95% confidence intervals were as the follows: acylcholines [0.40 (0.31, 0.50)], aromatic hydrocarbon derivatives [0.33 (0.22, 0.47)], sphingolipids [0.46 (0.33, 0.64)], tricarboxylic acid (TCA) cycle amino acids/peptides [0.39 (0.25, 0.62)], branched-chain amino acid metabolites [4.1 (2.9, 6.0)], acylcarnitines [1.8 (1.3, 2.5)], and TCA cycle/energy metabolites [2.0 (1.4, 3.0)]. The AHA-DS was only significantly associated with the acylcholine metabolites cluster [β (standard error) = 0.01 (0.004) SD increase in cluster score, p=0.02]. Conclusions: In individuals of PR descent, we identified a cluster of acylcholine metabolites where concentrations are higher among those with better diet quality and lower among those with prevalent T2D.

Gut mycobiome and its interaction with diet, gut bacteria and alzheimer's disease markers in subjects with mild cognitive impairment: A pilot study.

BackgroundRecently, we reported that patients with mild cognitive impairment (MCI) harbor specific signature of bacteria in their gut and that a modified Mediterranean ketogenic diet (MMKD) improves Alzheimer's disease (AD) markers in cerebrospinal fluid (CSF) and the signatures of gut bacteria. However, other microbial population such as gut fungi (mycobiome) in relation to MCI/AD pathology, gut bacteria and diet remain unknown.MethodsWe measure gut mycobiome by sequencing of the fungal rRNA ITS1 gene in 17 older adults (11 MCI; 6 cognitively normal [CN]) in a single-center, randomized, double-blind, crossover pilot study, before and after 6 weeks intervention of MMKD and American Heart Association Diet (AHAD), and determine its correlation with AD markers in CSF and gut bacteria.FindingsCompared to CN counterparts, patients with MCI have higher proportion of families Sclerotiniaceae, Phaffomyceteceae, Trichocomaceae, Cystofilobasidiaceae, Togniniaceae and genera Botrytis, Kazachstania, Phaeoacremonium and Cladosporium and lower abundance of Meyerozyma. Specific fungal taxa exhibit distinct correlation arrays with AD markers and gut bacteria in subjects with versus without MCI. MMKD induces broader effect on fungal diversity in subjects with MCI and increases Agaricus and Mrakia while decreasing Saccharomyces and Claviceps with differential response in subjects with or without MCI.InterpretationThe study reveals MCI-specific mycobiome signatures and demonstrates that distinct diets modulate the mycobiome in association with AD markers and fungal-bacterial co-regulation networks in patients with MCI. The findings corroborate the notion of considering gut mycobiome as a unique factor that can affect cognitive health/AD by interacting with gut bacteria and diet and facilitate better understanding of the AD and related microbiome, using unique diet or microbiome modulators.

Abstract 52: Plasma Metabolomic Signatures of the American Heart Association Diet Score: Findings From the Boston Puerto Rican Health Study

Introduction: Puerto Rican adults living on the US mainland tend to have poor quality diets and adverse cardiometabolic risk. Plasma metabolomic signatures reflect dietary intakes and variability in metabolic response to diet. Hypothesis: A plasma metabolomic signature reflecting adherence to the American Heart Association (AHA) dietary guidelines will be associated with cardiometabolic risk. Methods: We used LC/MS to measure plasma metabolites (&gt;700) among Boston Puerto Rican Health Study participants, aged 45-75 years, without (n=252) and with (n=254) type 2 diabetes (T2D). We calculated a modified version of a previously validated AHA diet score (AHA-DS), which included variety and amounts of fruits/vegetables, whole grains, fish, saturated fat, trans fat, sodium, and added sugars. We used elastic net regression to identify a metabolomic signature that associated with higher adherence to the AHA-DS among those without T2D (training set) and replicated the associations among those with T2D (testing set). A metabolomic score was calculated as the weighted sum of the diet associated metabolites. We used general linear models to determine the cross-sectional associations between the AHA-DS, metabolomic score, and cardiometabolic risk factors. Results: A diet-associated metabolomic signature with 58 metabolites, primarily lipids and amino acids, was identified. This metabolomic score correlated moderately with the AHA-DS among those with and without T2D (r=0.42-0.46, P &lt;5.7x10 -12 ). In all participants (n=506), the metabolomic score, but not the AHA-DS, was significantly associated with higher HDL-C and LDL-C concentrations, and lower waist circumference ( P &lt;0.004; Table 1). No associations were observed for triglyceride concentrations, glycemia measures, or blood pressure. Conclusions: In individuals of Puerto Rican descent, we identified a metabolomic signature that reflected adherence and metabolic response to the AHA dietary guidelines and that associated with cardiometabolic risk factors.

Modified ketogenic diet is associated with improved cerebrospinal fluid biomarker profile, cerebral perfusion, and cerebral ketone body uptake in older adults at risk for Alzheimer’s disease: a pilot study

There is currently no established therapy to treat or prevent Alzheimer’s disease. The ketogenic diet supplies an alternative cerebral metabolic fuel, with potential neuroprotective effects. Our goal was to compare the effects of a modified Mediterranean-ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) on cerebrospinal fluid Alzheimer’s biomarkers, neuroimaging measures, peripheral metabolism, and cognition in older adults at risk for Alzheimer’s. Twenty participants with subjective memory complaints (n = 11) or mild cognitive impairment (n = 9) completed both diets, with 3 participants discontinuing early. Mean compliance rates were 90% for MMKD and 95% for AHAD. All participants had improved metabolic indices following MMKD. MMKD was associated with increased cerebrospinal fluid Aβ42 and decreased tau. There was increased cerebral perfusion and increased cerebral ketone body uptake (11C-acetoacetate PET, in subsample) following MMKD. Memory performance improved after both diets, which may be due to practice effects. Our results suggest that a ketogenic intervention targeted toward adults at risk for Alzheimer’s may prove beneficial in the prevention of cognitive decline.